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Peripheral pulmonary wedge angiography in chronic obstructive pulmonary disease. Relationship to pulmonary function, chest x-ray film, and hemodynamic data.

Peripheral pulmonary wedge angiographic studies can investigate only limited areas of the pulmonary vascular bed; nevertheless, this technique is very useful in emphasizing the morphologic changes of small vessels (less than 1 mm in diameter) in pulmonary emphysema. The aim of this work is to determine the relationship between peripheral wedge angiographic appearances and pulmonary function, the chest x-ray film, and hemodynamic data in patients with chronic obstructive pulmonary disease. Three healthy subjects, four patients with type-A chronic obstructive pulmonary disease, and eight patients with type-B chronic obstructive pulmonary disease were studied. Among the tests of pulmonary function, only a marked reduction (less than 60 percent of predicted) of the diffusing capacity for carbon monoxide is always indicative of severe widespread emphysema. No relationship was found between hemodynamic data and peripheral wedge angiographic findings. Some agreement resulted between the chest x-ray film and peripheral wedge angiographic abnormalities only in patients with type-A chronic obstructive pulmonary disease; on the contrary, in patients with type-B chronic obstructive pulmonary disease, both false-positives and false-negatives were noted.

Angiography↗

The spirographic "kink". A sign of emphysema.

The significance of the "kink" occurring in the early portion of the forced expiratory spirogram of some patients with obstructed airflow was investigated in 153 patients with chronic obstructive pulmonary disease or asthma. The kink, which is presumably due to airway collapse, is facilitated by the presence of emphysema, which results in loss of elastic recoil, a positive pleural pressure, high bronchiolar resistance, and structural weakness in the walls of the major airways. A significant reduction of carbon-monoxide diffusing capacity was used as the indicator of the presence of significant anatomic emphysema. Eighty percent (39) of 49 patients with the spirographic kink had a low diffusing capacity, whereas only 16 of those without the kink had significantly impaired diffusion. Seventy percent (39) of the 56 patients who had emphysema by this criterion demonstrated a spirographic kink. This test is, therefore, offered as a simple, effective, and widely applicable screening procedure for detecting emphysema, with a low incidence of false-positive results.

Asthma↗

Cost-effectiveness of nuclear medicine procedures in renovascular hypertension.

The role of nuclear medicine in the differential diagnosis of renovascular hypertension (RVH) has been a highly controversial one. The reason for this rests with the lack of specificity of this test in screening for RVH. Although renography is very sensitive in detecting unilateral renal disease, it is nonspecific and an unacceptable number of false-positives occur. Recently the introduction of captopril renography has provided a new stimulus for reevaluation of this test in the differential diagnosis of renovascular disease. In spite of prevailing opinion, a careful review of the relative cost of renography and digital subtraction angiography (DSA) demonstrates that there is a role for renography in this differential diagnosis at all stages of investigation. Routine renography, when interposed between DSA studies, significantly reduces the cost per case of RVH found. If captopril renography proves as specific as is theoretically possible, the cost reductions achieved can be even greater. There is a significant and cost-efficient role for renography in the differential diagnosis of RVH. In addition to its reduction of cost in case finding, renography also avoids the risk of contrast media administration in a significant number of patients by reducing the population for screening to those at very high risk of disease.

Angiography↗

Plasma abnormal prothrombin (des-gamma-carboxy prothrombin) as a marker of hepatocellular carcinoma.

Des-gamma-carboxy prothrombin [DCP], a protein induced by vitamin K absence or antagonist-II and also abbreviated PIVKA-II, was evaluated as a serologic marker for hepatocellular carcinoma (HCC). Its plasma levels were measured by enzyme immunoassay (E-1023) using an anti-DCP monoclonal antibody in 514 patients with various diseases. Of 120 patients with HCC, 76 (63%) had abnormal DCP levels greater than 0.1 arbitrary unit (AU)/ml and 58 (48%) showed levels greater than 0.3 AU/ml. When a diagnostic minimum level of 0.3 AU/ml was applied for DCP, false-positive cases of HCC were virtually eliminated. In some patients with HCC, plasma DCP levels normalized after surgical resection of the tumor. However, they rose again later with recurrence of the disease. The sensitivity of DCP in the diagnosis and monitoring of HCC was increased by serial and simultaneous determinations of alpha-fetoprotein (AFP), because high DCP levels were observed more often in low AFP-producing HCC patients. Elevated plasma DCP levels were not related to low vitamin K concentration in the serum. In fact, in many patients vitamin K administration resulted in only a moderate reduction of DCP levels. These results suggested strongly that DCP was synthesized by the hepatoma cells.

Adenoma, Bile Duct↗

An appraisal of the nitroblue tetrazolium reduction test.

The available literature on the nitroblue tetrazolium reduction test is reviewed. The mechanism of this test is poorly understood. There are two basic methods of performing the test, namely, the stimulated and the spontaneous methods. However, the test procedure has not been standardized, and numerous modifications have ensued resulting in a number of technics. The stimulated test has proved to be valuable for screening patients or carriers with chronic granulomatous disease of childhood. It is one of the useful tests in studying neutrophil dysfunction. On the other hand, extensive accumulated data indicate that this test, be it stimulted or spontaneous, cannot be relied upon as an absolute test to differentiate bacterial from nonbacterial infectious disease as there have been numerous false-positive and false-negative results. When this test is used, the result should be interpreted in the context of other laboratory test results and the clinical picture of the patient. Preliminary data indicate that in certain diseases, if the initial test is positive in a particular patient, it may be useful as one of the follow-up tests to ascertain the activity of the disease process.

Bacterial Infections↗

Cytodiagnosis and other methods of biopsy in the modern management of breast cancer.

Since 1970 fine-needle aspiration cytology for breast tumours has grown in popularity and is now routinely used in the initial diagnosis of palpable breast masses in the United States and other parts of the world. Fast staining methods of the aspirate enables reporting within 10 minutes of the aspirate being performed. Training and experience is important in obtaining satisfactory smears for diagnosis, and pitfalls are false-negative and false-positive findings, which may have dire consequences for the patient if cytological diagnosis is the final arbiter. Conditions such as benign mammary dysplasia and sclerosing adenosis are the most common sources of highly cellular smears and often show marked atypia, which makes distinction from carcinoma difficult. Also, atypical papillary formations present a diagnostic problem, and biopsy is indicated to exclude a papillary carcinoma. Fine-needle aspirations very seldom cause traumatic complications, and these are usually of a minor degree. Seeding along the needle track has occurred, but in most cases with a larger-caliber (18 s.e.g.) needle. Aspiration itself has been shown to have no effect on the survival rates in breast carcinoma. Contemporary reports show that around 90% of cases of breast cancer can be detected with confidence by means of this procedure. The reduction in scar formation facilitates future evaluation of the patient as scar tissue often interferes with the interpretation of mammograms. Cost effectiveness is evident in terms of decreased use of anaesthetics and operating time and a reduction in the use of frozen section histology by about 80%.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗

Immunogenic effects of culture-derived exoantigens of Cooperia punctata on calves before and after challenge exposure with infective larvae.

The parasitic stages of Cooperia punctata were cultivated in vitro, and the incubation fluid from these stages containing exoantigen (ExoAg; metabolites, secretions, excretions) was diafiltered (retaining material of approximate molecular weight greater than 10,000), concentrated, and lyophilized. Using serum of calves immune to C punctata, ExoAg activity was verified by agar gel immunodiffusion. The ExoAg was combined with adjuvants and was inoculated into calves. Results of preliminary experiments indicated that the ExoAg had potent biological activity capable of inducing severe respiratory distress and death. Subsequently, however, improved inoculation procedures and combination of ExoAg with aluminum hydroxide gel or Freund complete adjuvant consistently prevented this reaction in 25 calves. In helminth-free calves, the ExoAg induced marked eosinophilia, which generally was greater during the ExoAg-exposure period than after challenge exposure with infective larvae. Of 27 calves exposed to the various ExoAg inoculation schedules, 12 had nematode reductions greater than 80%, 10 had less than 16% reduction, and 5 had reductions between 39 and 72%. This polarization of the nematode recovery data generally thwarted statistical difference in overall consideration of all ExoAg inoculation schedules. Additional manifestations of resistance, ie, prolonged prepatent period, reduced patent period, reduced number or lack of nematode eggs passed in feces, and reduced nematode length, were observed in calves of certain ExoAg inoculation schedules. In vitro blastogenic responses of blood lymphocytes was observed in calves exposed to ExoAg. Quantitatively, this cell-mediated immune response to ExoAg was as great as or greater than that after subsequent challenge exposure with infective larvae. Intradermal inoculation of ExoAg into a calf resistant to C punctata induced delayed-type hypersensitivity. However, this reaction to ExoAg was not observed in nonimmunized, helminth-free calves used as controls. Humoral antibodies against ExoAg were detected by an agar gel immunodiffusion test. Calves exposed to ExoAg always seroconverted and usually remained seropositive until necropsy. There were no false-positive results; however, ExoAg did not consistently coprecipitate (by agar gel immunodiffusion) with serum from infected calves that were not exposed to ExoAg.

Animals↗

Role of 67gallium citrate scanning in the management of non-Hodgkin's lymphoma.

67Gallium scans were performed as part of the initial evaluation in 45 patients with non-Hodgkin's lymphoma. Eighteen of these patients underwent staging laparotomy and splenectomy. In addition, scans were performed either shortly after therapy was completed or during subsequent followup in 10 patients. The initial scans were found most useful for patients with histiocytic lymphoma: in detecting sites of involvement above the diaphragm and the high para-aortic/mesenteric region, and when tumors were greater than 2 cm in diameter. The addition of 67Ga scanning to the pre-operative clinical evaluation reduced the number of incorrectly staged patients from 8 to 4. Reversion of previously positive 67Ga scans to negative in 3 patients with suspected persistent or recurrent disease was associated with fibrosis and no lymphoma when biopsied. Five other patients had histologically documented positive 67Ga scans post-therapy; in 1 the 67Ga scan was only definitive noninvasive procedure. Despite the occurrence of both false-positive and false-negative 67Ga scans, this procedure appears to be a useful supplement to the pretreatment evaluation of patients with non-Hodgkin's lymphoma, especially the histiocytic form. Confirmation of its ability to detect high para-aortic/mesentric involvement may subsequently result in a reduction of the number of staging laparotomies necessary. For the post-treatment followup of these patients 67Ga scans may prove to be valuable noninvasive investigation.

Abdominal Neoplasms↗

The redox-cycling assay is not suited for the detection of pyrroloquinoline quinone in biological samples.

Based on the results of the so-called redox-cycling assay it has been claimed that various common foods and beverages as well as mammalian body fluids and tissues contain substantial quantities (microM) of free PQQ [M. Paz et al. (1989) in: PQQ and Quinoproteins (J.A. Jongejan and J.A. Duine, eds.) Kluwer Academic Publishers, Dordrecht, pp. 131-143 and J. Killgore et al. (1989) Science 245, 850-852]. However, by investigating samples from such sources with a biological assay of nM sensitivity, we could not confirm these claims. Analysis of the samples with procedures that proved adequate for the detection of PQQ adducts and conjugates gave equally negative results. To account for the positive response in the redox-cycling assay, as opposed to the negative results obtained by other methods, a search was made for those substances in these samples that caused the false-positive reactions. It was found that a number of commonly occurring biochemicals like ascorbic and dehydroascorbic acid, riboflavin and to a lesser extent pyridoxal phosphate, gave a positive response in the redox-cycling assay. The amounts of these interfering substances that were determined in the samples by independent methods could well explain the response. In separate experiments it was found that the effect of PQQ added to biological samples was obscured over an appreciable range of concentrations. For these reasons it must be concluded that the redox-cycling assay is not suited for the detection of PQQ in these samples. Any claims that are based on the results of this method should be disregarded.

Animals↗

Effects of pulmonary emphysema on QRS infarct size score.

Pulmonary emphysema can produce false-positive electrocardiographic (ECG) changes of anterior myocardial infarction (MI). This problem was not addressed in earlier studies of the Selvester 54 Criteria/32 Point QRS score for MI size. The purpose of this study was to examine an automated Hewlett Packard ECG Computer Language (HP-ECL) implementation of the QRS score in the following groups of subjects. Patients who had been studied for possible lung disease with pulmonary tests, including lung volumes, were divided into two groups: group 1 (n = 133), with abnormal tests (emphysema); and group 2 (n = 102), with normal tests (no emphysema). Two other groups were studied: group 3 (positive controls, n = 44), with greater than 3 QRS points for MI on ECG and documented coronary disease with wall motion abnormalities on angiography; and group 4 (negative controls, n = 146), 49 house staff and 97 clinically normal men. A frontal plane P axis greater than 65 separated 90% of patients with emphysema from those without. Of 133 patients with emphysema, 60 (45%) had greater than 3 QRS points for MI on ECG, mainly from Q criteria in aVL and V1-V3; decreased R criteria 1 in V2, V3, and V6; and abnormal R/S criteria in V4-V6. Using HP-ECL, the QRS score was readily modified so that when P axis was greater than 65 these MI size criteria were suppressed. This resulted in a more appropriate incidence of MI diagnoses: 2% (down from 45%) in emphysema patients, no change in specificity, and minor reduction in sensitivity to MI in infarct controls from 100% to 96%.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography↗

Successful use of pooled sera to determine HIV-1 seroprevalence in Zaire with development of cost-efficiency models.

To determine the accuracy and cost efficiency of pooling sera prior to HIV-1 testing, sera from 8,000 Kinshasa factory workers and their spouses were screened individually (2.44% seropositive) and in 800 pools of 10 sera each. There were no false-negative or false-positive pools, resulting in a calculated seroprevalence estimate of 2.42%. Further testing of all sera in positive pools can identify HIV-positive individuals. These applications were modeled to compare the cost-efficiency of pooling with individual testing under different conditions. The results suggest that pooling provides an alternative test format for use in both developing and industrialized countries when the seroprevalence and/or the marginal cost of obtaining a sample are sufficiently low. For our cohort, testing only the pools for seroprevalence estimation resulted in a 78% cost saving compared with individual testing; pooling with subsequent identification of individual seropositives represented a 56% cost reduction.

Acquired Immunodeficiency Syndrome↗

A clinic-based system for monitoring the quality of techniques for the diagnosis of gonorrhea.

The author describes a clinic-based system that monitors the quality of techniques for diagnosis of gonorrhea by continuous comparison of the results of gram-strained smears of urethral and cervical specimens with the corresponding cultures. Discrepant results are immediately reviewed. During a two-year period, the system detected two defects in culture incubation, visual defects in a laboratory technician, and three unexplained reductions in cultural sensitivity. The system motivates clinicians and laboratory technicians to maintain a high level of quality control. In 11,474 comparisons of urethral smear and culture results, there was agreement in 96.9% while the smear alone was positive in 1.6% and the culture alone in 1.5%. Review of positive-smear-negative-culture discrepancies indicated that most smears judged "false-positive" were so classified on the basis of false-negative cultures. In study of 1,331 women, the endocervical smeras identified 60% (273/455) of those with positive culture discrepancies. Many of these may have represented false-negative cultures.

Clinical Laboratory Techniques↗

False-positive, follicular and irritant patch test reactions to metal salts.

853 hard metal workers were patch tested with nickel sulphate 5%, potassium dichromate 0.5% and cobalt chloride 1%, each in petrolatum. Non-allergic reactions appeared in 6.5% of the nickel tests, 13% of the chromium tests and 18.3% of the cobalt tests. Most of the individuals with positive, poral or pustular reactions were retested with serial dilutions of metal salts in pet. and in water. The accuracy of a positive initial nickel reaction was 83%, a chromium reaction 40% and a cobalt reaction 62%. The nonallergic reactions were partly reproducible and correlated with both the type of patch test material and with individual factors. Weak and moderately strong positive patch test reactions to metal salts may be irritant and should be checked with serial dilution tests or at least be retested. A reduction of the cobalt chloride concentration from 1% to 0.5% in the standard test material is discussed.

Chromates↗

Results of ophthalmosonometry and supraorbital photoplethysmography in evaluating carotid arterial stenoses.

A total of 263 patients underwent either periorbital ophthalmosonometry (Doppler ultrasound) or a combination of ophthalmosonometry and supraorbital photoplethysmography (SOPPG) to determine the presence or absence of a hemodynamically significant lesion (occlusion or greater than 50% reduction in lumen diameter). There were 522 vessels studied with Doppler ultrasound and 272 vessels with a combination of the two modalities. The tests were correlated with carotid arteriography to determine their accuracy. Overall accuracy of the Doppler ultrasound examination was 95%. A normal Doppler ultrasound examination was obtained in 367 vessels and arteriography confirmed the absence of a hemodynamically significant lesion in 93%. Of 155 vessels with an abnormal Doppler examination, 149 (96%) were proven on arteriography to have hemodynamically significant lesions. The Doppler ultrasound examination had a high incidence of false-negative examinations (26%) in those vessels that were between 50% and 99% stenotic, however. The SOPPG alone had a high incidence of false-positive examinations (19%); however, in 155 vessels with a normal SOPPG, 98% were proved to have no hemodynamically significant lesion. The combination of Doppler ultrasound and SOPPG was highly accurate in identifying patients with hemodynamically significant lesions. Of 97 vessels with such lesions, 96 (99%) had either an abnormal Doppler ultrasound examination or an abnormal SOPPG. In 240 vessels with concordant results of the Doppler ultrasound and SOPPG, the presence or absence of a hemodynamically significant lesion was accurately predicted in 235 (98%).

Arterial Occlusive Diseases↗

Evaluation of the usefulness of nitroblue tetrazolium reduction test (NBT test) for detection of bacterial infection in cancer patients.

False positivity of the NBT test in neoplastic diseases described by some authose may be a limitation in the use of the test for infection screening in cancer patients. For explaining this problem studies were performed in a group of 30 patients with various untreated malignancies without infection and in 20 of these with bacteriologically confirmed infections. The obtained results were compared with those in groups of normal persons without and with infection. Slightly modified Park method for spontaneous and stimulated NBT test was used. No significant differences between patients of both groups without infection were found. The increase in positivity of the test in presence of infection was lower in cancer patients than in normal subjects, however, it was non-significant. We did not observe any false-positive results in our patients, though one case of false negativity in myeloma is described separately. It is concluded that neoplastic disease does not cause, as such positivity of the NBT test. Because of similar response of NBT test to presence of infection, the NBT test is recognized as very useful for infection screening in cancer patients similarly as in normal persons.

Adult↗

[Echographic measuring of the length of the fetal femur in the screening for Down syndrome].

OBJECTIVE: Our purpose was to assess the value of sonographic measurement of fetal femur length in the second trimester, as a screening tool for Down's syndrome. STUDY DESIGN: We evaluated a consecutive series of fetuses scanned by a single sonologist at the time of amniocentesis between 15 and 19 weeks. The study group consisted of fetuses with Down's syndrome (N = 16); the control group comprised normal fetuses (N = 1163). A linear regression model of the normal femur length based on biparietal diameter (BPD), was established for our population; the ratios of measured to expected femur length for a viven BPD (FL M/E) were calculated in the two groups. To test statistical significance of observed differences between case and control population, unpaired t test was used. The ability of specific FL M/E cut-off values to discriminate between Down syndrome and normal fetuses was assessed by Fisher's exact test. RESULTS: The mean ratio of measured to expected femur length was significantly lower in the Down syndrome as compared with control population (0.9473, DS 0.0795) versus 1.0, DS 0.0745) (p < 0.0045). The ratio of 0.91 or less predicted Down's syndrome with a sensitivity of 43.7% and a false-positive rate of 8.6%. For women with risk of one in 250 and one in 1000 of having an affected fetus based on maternal age, a shortened femur yielded positive predictive values of one in 26 and one in 105, respectively. CONCLUSION: These results suggest that the sonographic measurement of fetal femur length for the screening of Down syndrome in the low-risk population is hindered by a high false positive rate (about 9%). It follows that the percentage of women requiring an amniocentesis would increase to un unacceptably high level. The utilization of this biometric marker may be helpful, in our opinion, for identifying fetuses at risk for Down syndrome in women between 35 and 38 years of age. These women in fact, are not offered amniocentesis for the prenatal diagnosis of Down's syndrome in the majority of italian institutions. The sonographic measurement of fetal femur length could detect about 45% of fetal Down's syndrome, offering an amniocentesis to 9% of women, with a consequent reduction of the cost required. Only a prospective study can evaluate the efficacy of this method to predict Down syndrome in such group of women.

Adult↗

[Measuring temporal transmission properties of the visual system. Diagnostic value in suspected optic nerve neuritis].

The temporal transfer properties of the visual system were examined in 157 patients with suspected acute optic neuritis or papillitis. Foveal modulation sensitivity was measured as a function of temporal frequency (DeLange curve) both for the affected eye and the unaffected fellow eye. Patients with acute optic neuritis typically show a reduction of foveal modulation sensitivity at all temporal frequencies, high temporal frequencies above 10 cps being more markedly affected. The aim of the present study was to determine the sensitivity and specificity of this simple psychophysical procedure for the diagnosis of neuritis or papillitis in a reasonably large population of patients with suspected acute optic neuritis or papillitis. In each case the final diagnosis was confirmed by evaluation of the clinical signs and symptoms, the course of disease and additional diagnostic procedures, e.g. electrophysiology, perimetry, neurological examination including CT, lumbal puncture and examination of cerebrospinal fluid. In 136 cases (86.6%) the result read from the DeLange curve was correctly positive or negative. In 17 cases (10.8%) the DeLange curve indicated a false-positive and in 4 cases (2.6%), a false-negative result.

Flicker Fusion↗

Strategies for screening blood for human immunodeficiency virus antibody. Use of a decision support system.

A decision analytic model was used to examine alternative strategies to screen donated blood for human immunodeficiency virus (HIV) using data from the literature and from 1987 blood-screening programs in areas with high and low prevalence of HIV. Sensitivity analyses incorporated uncertainties about HIV infection and test performance. Current screening strategies are estimated to allow 20.5 infected units per million donated units to be transfused at a cost of $16,850 per HIV-positive unit detected in high-prevalence areas and 4.7 infected units per million donated units to be transfused at a cost of $32,275 per HIV-positive unit detected in low prevalence areas, with nine false-positive notifications of uninfected patients per million units screened and 14.9 discarded, noninfected units per HIV-positive unit in low-prevalence areas. Testing donated blood for HIV can be improved by individualizing screening strategies for areas with different prevalences of HIV. Efforts to further reduce transfusion-associated HIV should focus on improved test performance in early stages of infection, reduction of unnecessary transfusions, donor recruitment in lower-risk groups, and public health measures to reduce HIV infection among the general population.

Blood Donors↗